Muscle Cell Types: Structure and Function

Muscle Cell Types: Structure and Function

• Skeletal muscle is attached to the skeleton and is under voluntary control.
• Skeletal muscle cells are large, unbranched, striated fibers innervated by motor neurons.
• T-tubules in skeletal muscle are located at Z-lines, and they form triads with the sarcoplasmic reticulum (SR).
• Cardiac muscle is found in the heart walls (myocardium) and operates involuntarily.
• Cardiac muscle cells are branched, brick-shaped, striated, and connected by intercalated discs with gap junctions.
• Cardiac muscle cells have dyads (1 T-tubule + 1 SR terminal cisterna) and are rich in mitochondria.
• Cardiac muscle action potentials are long (200–400 ms) to prevent tetany.
• Smooth muscle is present in blood vessels and organs, contracting involuntarily and slowly.
• Smooth muscle cells are spindle-shaped, lack striations due to irregular actin/myosin arrangement, and have sparse SR without T-tubules.
• Smooth muscle excitation can occur via action potentials or graded depolarizations.

Membrane Potential and Excitation

• Neuronal action potentials are short (~1 ms) for rapid signaling, while skeletal muscle action potentials are ~2–5 ms, enabling tetany.
• Cardiac action potentials have a long duration (200–400 ms) with a plateau phase due to L-type Ca²⁺ channels, preventing re-entry arrhythmias.
• Smooth muscle excitation involves voltage-gated L-type Ca²⁺ channels opening upon depolarization, leading to contraction.
• Smooth muscle excitation can be triggered by agonists activating receptors, leading to IP₃ production and SR Ca²⁺ release.

Excitation-Contraction Coupling (ECC) in Skeletal Muscle

• Neuromuscular activation begins with a motor neuron releasing ACh, which binds to nicotinic receptors, causing Na⁺ influx and depolarization.
• The action potential propagates along the sarcolemma and into T-tubules.
• T-tubule depolarization causes a conformational change in L-type (DHPR), mechanically opening RyR1 on the SR.
• Ca²⁺ is released from the SR, and no extracellular Ca²⁺ is required.
• Ca²⁺ binds to troponin C, causing a tropomyosin shift, which leads to cross-bridge cycling and contraction.
• Relaxation occurs when SERCA pumps resequester Ca²⁺ back into the SR.
• The triad structure facilitates rapid, voltage-induced Ca²⁺ release in skeletal muscle.

Excitation-Contraction Coupling (ECC) in Cardiac Muscle

• Cardiac muscle contraction begins with SA node depolarization spreading via gap junctions.
• The action potential plateau phase activates L-type channels, allowing Ca²⁺ entry ("trigger Ca²⁺").
• Ca²⁺ binds to RyR2, causing a massive release of Ca²⁺ from the SR (CICR).
• Ca²⁺ interacts with troponin C, resulting in cross-bridge cycling and contraction.
• SERCA (regulated by phospholamban) and NCX remove Ca²⁺ during relaxation.
• Cardiac muscle ECC depends on extracellular Ca²⁺, as its removal stops contraction rapidly (in milliseconds).

Excitation-Contraction Coupling (ECC) in Smooth Muscle

• Vascular smooth muscle contraction occurs when depolarization opens L-type channels, leading to Ca²⁺-calmodulin activation, MLCK activation, myosin phosphorylation, and contraction.
• Visceral smooth muscle contraction is initiated by an agonist binding, activating Gq, PLC, IP₃ production, SR Ca²⁺ release, and calmodulin activation.
• Relaxation in smooth muscle involves myosin phosphatase dephosphorylating myosin and K⁺ channel opening, which hyperpolarizes the cell.
• Smooth muscle uses calmodulin as the Ca²⁺ sensor instead of troponin.
• Smooth muscle has plasticity, which is a latch state that allows sustained contraction.

Comparative Summary of ECC Features

• Skeletal muscle relies on the SR as its Ca²⁺ source (voltage-induced), cardiac muscle relies on the SR (CICR) and extracellular Ca²⁺, and smooth muscle relies on the SR (IP₃) or extracellular Ca²⁺.
• The key channel in skeletal muscle is the DHPR-RyR1 mechanical link, in cardiac muscle it is L-type + RyR2, and in smooth muscle it is L-type or IP₃ receptors.
• The structural unit in skeletal muscle is the triad, in cardiac muscle it is the dyad, and in smooth muscle it is caveolae (no T-tubules).
• The Ca²⁺ sensor is troponin C in both skeletal and cardiac muscle, while it is calmodulin in smooth muscle.
• Relaxation is mediated by SERCA in skeletal muscle, SERCA + NCX in cardiac muscle, and myosin phosphatase in smooth muscle.

Clinical and Physiological Insights

• L-type blockers (verapamil) can reduce cardiac contractility.
• Ryanodine can lock RyR2 in either open or closed states.
• Hypertension can result from excessive Ca²⁺ entry, causing vasoconstriction.
• Asthma can be related to IP₃-mediated bronchoconstriction.

Key Distinctions in Muscle Function

• Skeletal muscle has rapid, voluntary contractions via direct DHPR-RyR1 coupling.
• Cardiac muscle has involuntary, CICR-dependent contractions, resistant to tetany.
• Smooth muscle has dual pathways (voltage/ligand-gated) and is adaptable to sustained contractions.